Tributylphosphine → t-Butyl 3-[3-(benzenesulphonylmethyl)-6-(furan-3-yl)-2-(methoxycarbonyl)phenoxy]azetidine-1-carboxylate

HRID 2177820Notes

Reaction equation

HRID 2177820 reaction equation
[CH2:1](P(CCCC)CCCC)CCC.N(C(OC(C)C)=O)=NC(OC(C)C)=O.[C:28]1([S:34]([CH2:37][C:38]2[C:43]([C:44]([OH:46])=[O:45])=[C:42]([OH:47])[C:41]([C:48]3[CH:52]=[CH:51][O:50][CH:49]=3)=[CH:40][CH:39]=2)(=[O:36])=[O:35])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[C:53]([N:60]1[CH2:63][CH:62](O)[CH2:61]1)([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54]>C1COCC1.O.C(OCC)(=O)C>[C:28]1([S:34]([CH2:37][C:38]2[C:43]([C:44]([O:46][CH3:1])=[O:45])=[C:42]([C:41]([C:48]3[CH:52]=[CH:51][O:50][CH:49]=3)=[CH:40][CH:39]=2)[O:47][CH:62]2[CH2:63][N:60]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:61]2)(=[O:36])=[O:35])[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

8

Reactant 4

HCID 13831TributylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylateHCID 52914186HCID 52914186, compound2×

Product 1

HCID 67107519t-Butyl 3-[3-(benzenesulphonylmethyl)-6-(furan-3-yl)-2-(methoxycarbonyl)phenoxy]azetidine-1-carboxylateYield 429.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Tri-n-butylphosphine (0.087 g) was added dropwise to a solution of di-isopropyl azodicarboxylate (0.099 g) in dry THF (2 ml) at 0° C. The mixture was warmed to room temperature for 10 minutes then re-cooled to 0° C. A mixture of methyl 6-(benzenesulphonylmethyl)-3-(furan-3-yl)-2-hydroxybenzoate (Intermediate 114, 0.05 g) and N-Boc-azetidin-3-ol (0.045 g) in THF (1 ml) was added dropwise and then the reaction mixture was warmed to room temperature for 10 minutes then heated to 55° C. for 6 hours. After cooling, ethyl acetate and water were added and the organic layer was separated, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane (1:3) to give t-butyl 3-[3-(benzenesulphonylmethyl)-6-(furan-3-yl)-2-(methoxycarbonyl)phenoxy]azetidine-1-carboxylate (0.316 g) as a gum.

Workup

  1. temperaturethen re-cooled to 0° C
  2. additionwas added dropwise
  3. temperaturethe reaction mixture was warmed to room temperature for 10 minutes
  4. temperaturethen heated to 55° C. for 6 hours
  5. temperatureAfter cooling
  6. customthe organic layer was separated
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customThe filtrate was evaporated to dryness
  10. customthe residue was purified by chromatography on silica
  11. washeluting with a mixture of ethyl acetate and cyclohexane (1:3)

Sources & evidence

ORD record
ord-cea928f371eb40e4b691a1d5d346d61b
Source dataset
uspto-grants-2015_06
Patent number
US09067905B2

Reaction notes

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